Incidence of lingual nerve damage following surgical extraction of mandibular third molars with lingual flap retraction: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to examine more recent data to determine the extent of lingual nerve injury (LNI) following the surgical extraction of mandibular third molars (M3M). A systematic search of three databases [PubMed, Web of Science and OVID] was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria encompassed studies on patients who underwent surgical M3M extraction using the buccal approach without lingual flap retraction (BA-), buccal approach with lingual flap retraction (BA+), and lingual split technique (LS). The outcome measures expressed in LNI count were converted to risk ratios (RR). Twenty-seven studies were included in the systematic review, nine were eligible for meta-analysis. Combined RR for LNI (BA+ versus BA-) was 4.80 [95% Confidence Interval:3.28–7.02; P<0.00001]. The prevalence of permanent LNI following BA-, BA+ and LS (mean%±SD%) was 0.18±0.38, 0.07±0.21, and 0.28±0.48 respectively. This study concluded that there was an increased risk of temporary LNI following M3M surgical extractions using BA+ and LS. There was insufficient evidence to determine whether there is a significant advantage of BA+ or LS in reducing permanent LNI risk. Operators should use lingual retraction with caution due to the increased temporary LNI risk.


Introduction
Lingual nerve injury (LNI) can have a detrimental effect on a patient's quality of life (QoL) [1]. It can occur as a result of iatrogenic injury following oral and maxillofacial surgery (e.g. orthognathic surgery) [2] and the removal of mandibular third molars (M3M) [3]. LNI can lead to complications such as altered touch and taste sensation, neuralgia, as well as impaired swallowing and speech [4]. LNI following M3M removal is usually transient, with studies reporting the chance of spontaneous recovery to be 60% and 35% at three and six months respectively [4]. When LNI lasts more than six months, there is a significantly lower chance of spontaneous recovery and may be considered permanent [5]. Bagheri et al. found that patients with LNI lasting longer than nine months have less than 10% chance of recovery [4]. The incidence of permanent LNI following the removal of M3M is approximately 0.04-0.6% [6]. Though the incidence of LNI is low, the severity of the complications is deemed significant enough that patients should be informed of the risk of LNI before the procedure.
The lingual nerve (LN) is a branch of the mandibular division of the trigeminal nerve [7]. It provides somatosensory innervation such as pain, thermal, and pressure sensation to the mucous membrane. The LN innervates the anterior two-thirds of the tongue, lingual gingiva of the mandibular teeth, and the mucosa of the floor of the mouth [7]. Approximately 1 cm below where the inferior alveolar nerve and LN separates, the LN is joined by the chorda tympani nerve [8]. The path of the LN varies between individuals. A study by Pogrel et al. found that, in twenty cadaveric heads, the LN was in a range of 1 to 7 mm away from the lingual plate of the M3M [9]. This highlights the potential risk of LNI when a lingual flap is retracted due to varying locations of the LN.
The traditional approach to surgically removing the M3M is through raising a buccal flap and removing buccal bone, which can be done without (BA-) or with (BA+) lingual retraction [10]. An alternative approach is raising a lingual flap, placing a lingual retractor, and removing lingual bone, known as the lingual split technique (LS) [11]. The use of a lingual retractor has been associated with a higher incidence of LN paraesthesia [12]. The argument for this technique is that the incidence of recovery is higher, as severing the LN is avoided by protecting it with instruments and retractors. For example, the flap can be raised using Molt's or Ward's curved periosteal elevator and retracted using Walter's lingual retractor [10]. Some also argue that lingual flap retraction provides improved access to the surgical site [10]. However, there are contrasting opinions. A systematic review, published in 2001, concluded that such retraction increased the tendency of temporary LNI [12]. However, this result was from analysing research performed pre-1999. Although there was a recent systematic review that was published [13], there is currently no published up-to-date study that quantitatively outlines the risks involved post-1999.
Therefore, this systematic review and meta-analysis aims to examine more recent data to determine the extent of LNI following the surgical removal of M3M. More specifically, comparing the incidence between three techniques: BA-, BA+, and LS.

Ethical approval
The systematic review was registered on the PROSPERO database (Registration number: CRD42020181836).

Study selection
The systematic review was registered on the PROSPERO database (Registration number: CRD42020181836) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14]. Two authors (J.L. and B.F.) independently conducted a systematic search of the literature in June 2022. The digital databases PubMed, Web of Science, and OVID were utilised to assess published studies that reported on the incidence of LNI following the surgical removal of M3M. Multiple searches were conducted using the following keyword combination: Firstly, "lingual nerve" AND buccal flap, retraction, oral surgery, third molar, lingual split. Secondly, "lingual nerve injury" AND buccal flap, retraction, oral surgery, third molar, lingual split. The connecting word 'AND' was used as a combination between the key words "lingual nerve" and "lingual nerve injury" and the rest of the search words. A limit was placed on the time of publication, with only articles published between May 1999 to June 2022 selected, as the previous landmark systematic review by Pichler and Beirne investigated studies from 1983 to May 1999 [12]. Grey literature was not assessed. All studies not in English were excluded. All studies except for systematic reviews were included. In the screening stage, the title and abstracts of publications were reviewed, and the duplicated studies were excluded. Subsequently, full-text copies were reviewed for eligibility for a systematic review. The inclusion criteria consisted of all studies on patients who have undergone surgical M3M extractions with BA-, BA+, or LS. Studies that did not meet the inclusion criteria were excluded. We utilised the software EndNote X9 (Clarivate, PA, USA) to organise the references and articles retrieved in the search. A consensus was reached after thorough discussion and gaining a third opinion from another author (J.P) if any discrepancies arose between the two examiners.

Selection criteria
Population: The population for this systematic review is patients who underwent the surgical removal of M3M Intervention/Comparison: The intervention was the extraction of M3M with or without lingual retraction or using the lingual split technique Outcome: The outcome being measured within our study was the incidence of lingual nerve injury following the surgical extraction of M3M Search outcome Fig 1 illustrates the outcomes of the search. From 2695 search results, 211 were excluded due to being outside the set time of publications, 1792 were removed due to being duplicates, 561 articles were excluded after analysing the title and a further 64 removed after analysing the abstract. Of the 67 potentially eligible studies, 40 citations were excluded. This left twentyseven studies meeting the criteria and being suitable for inclusion in this systematic review [10,. Of these, nine were suitable for quantitative synthesis and meta-analysis as information on LNI due to BA-, BA+, and LS was available [16,17,19,21,29,32,37,38,40].

Data extraction
The following were extracted: study design, prospective/retrospective design, number of patients, number of teeth, age of patients, location of study, intervention, types of lingual retractors used, comparison, outcomes, and quantitative data, which was the rate of lingual nerve injury, both permanent and temporary. The primary outcome was LNI. Within LNI, prevalence of temporary and permanent LNI was also calculated.

Data synthesis
The parameters for the meta-analysis consisted of analysing outcomes using the adopted risk ratio (RR) formula [41]: a = Number of LNI cases after BA+ b = Number of LNI cases BA-n 1 = Total number of cases after BA+ n 2 = Total number cases after BA-After obtaining the necessary parameters, a meta-analysis was undertaken in accordance with Review Manager software (RevMan 5.0 for Windows, Last Update-2014). The level of significance was set at 95% (P< 0.05). Statistical heterogeneity was determined based on the Tau-squared test, with a threshold P-value of 0.1 and inconsistency (I 2 ) test value greater than 50% indicating high heterogeneity [42].

Risk of bias
A critical appraisal tool to assess the quality of appropriate observation studies was utilised as per the checklist provided in the systematic review [43]. This included a series of questions with regards to the content of the Introduction, Methods, Results, Discussion, and Other sections. Furthermore, the cumulative count for these individual studies was tabulated.

Inter-agreement reliability
Inter-agreement reliability was calculated between the two independent reviewers, in the data extraction (identification, screening, eligibility, and inclusion) stage (%). In addition, kappa statistics as a measure to test the inter-agreement reliability amongst the reviewers was computed during the risk of bias stage [SPSS version 27.0 (IBM Company, Chicago, Il, USA)] [44]. Table 1 highlights the characteristics of all studies included in the systematic review. Except for six studies [22,30,32,33,36,37], all the studies were prospectively designed. Five of the prospective studies were randomised controlled trials [21,23,29,35,38]. There was a total number of 24,985 participants, aged between 12-89 years old, with 32,866 teeth analysed. Studies were undertaken in Australia, Brazil, China, Greece, Hong Kong, India, Jordan, Nigeria, Pakistan, Singapore, Spain, United Kingdom, and the United States. There was a total number of 388 cases of temporary LNI in the systematic review. In many studies the use of a lingual retractor was at the clinician's discretion and the type of lingual retractor used varied ( Table 2). Table 3 highlights the prevalence of temporary LNI as outlined by all studies [10,. Temporary LNI accounted for an average prevalence of 2.64%±2.25% standard deviation (SD). Table 4 highlights the prevalence of permanent LNI as outlined by all studies [10,. Permanent LNI accounted for an average prevalence of 0.24%±0.41%SD.

Meta-analysis
All studies that were included in the meta-analysis are outlined in Fig 2. Comparing BA+ vs BA-, the overall RR was 4.80 [95% Confidence Interval: 3.28-7.02; P < 0.00001], with a range of 3.13 to 34.50, and with negligible evidence of heterogeneity (I 2 = 0%). Table 5 outlines the assessment of the studies included in the systematic review according to AXIS [45]. Individual studies were provided in Supplement 1. All of the studies had a clear aim, appropriate risk factors and outcome variables measured to the aims of the study, discussions and conclusions justified by the results. None of the studies justified their sample sizes. There were only two studies that addressed non-responders [28,36], and only one study was internally consistent [20].

Discussion
To our knowledge, this is the most up-to-date study to quantitatively outline the possible risks involved in LNI following the surgical extraction of M3M. There was a statistically significant 4.80-fold increase in the risk of temporary LNI when BA+ was used compared to BA-. The incidence of permanent nerve injury was 0.28% with LS compared to 0.18% with BA-and 0.07% with BA+. Most of the articles did not provide sufficient information to develop a risk ratio for permanent injury. Zuniga et al. reported that the incidence of permanent LNI following the removal of M3M to be 0.04-0.60% regardless of the surgical technique [6]. Therefore, the findings in this study are not unusual. Further investigation to determine the incidence of permanent LNI is required so a meta-analysis can be conducted in the future. Various factors also affected the incidence of LNI. The most commonly found statistically significant risk factors in the literature were angulation of the teeth [16,19,20,26,46], operator's experience [17,20,25,26,29,46,47], and the difficulty of extraction (usually measured by the length of operation) [28,29,46,47]. Obiechina and colleagues stated that operating under general anaesthesia may be a risk factor as the tissues can be retracted more, leading to increased stretching causing lingual paraesthesia [34]. Other factors such as sectioning the tooth and removing bone may also increase the risk of LNI [16,26,46,47]. Age is also a suggested risk factor, however, whether or not this was statistically significant varied among the studies [16, 20, 24-26, 29, 36, 47]. The difficulty of extraction can be pre-operatively assessed by taking into account some of these identified risk factors, as well as the operator's clinical judgement.
A previous systematic review investigated the incidence of LNI following the use of three different techniques, BA-, BA+, LS [12]. Pichler and Beirne found that the incidence of temporary LNI was higher when LS was used versus BA+ when they were compared to BA-(RR-13.3 and 8.8 respectively). Permanent LNI was found to be the lowest when LS was used (0.10%) versus BA+ (0.60%), and BA-(0.20%) [12]. Rapaport and Brown also examined the LNI risk but grouped together all procedures that used a lingual retractor [13]. They determined that when a purpose-built instrument was used to retract lingually, the percentage risk of temporary LNI was lower versus no lingual retraction [0.56% vs 0.60% respectively]. Interesting to note is that the percentage risk of temporary LNI was 7.78% when a non-purpose  built instrument was used. The risk of permanent LNI was 0.00%, 0.08% and 0.41% for purpose-built lingual retraction, no lingual retraction and non-purpose built lingual retraction, respectively. Our study did not separate different types of retractors. A previous Cochrane review was conducted in 2020 analysing techniques for the removal of M3M [48]. This study found that the Peto Odds Ratio of permanent lingual nerve injury was 0.14 [0.00, 6.82] when comparing using a lingual retractor compared to not using one. However, this result was based on 1 study. The Odds ratio in the same Cochrane review for temporary lingual nerve injury when comparing the use of a lingual retractor with no lingual retractor was 4.18 [1.75, 9.98]. However, this was also only based on the results of 3 studies [48].
Our study showed that there was a statistically significant increased risk of temporary LNI when using BA+ versus BA-(RR = 4.80). The prevalence of temporary LNI following BA-, BA + and LS was found to be 1.24%, 2.39% and 2.44% respectively. This result was consistent with Pichler and Beirne. Their risk ratio when comparing BA+ and BA-was 8.8 and the prevalence of LNI was 0.60% (BA-), 6.40% (BA+), and 9.60% (LS). In both our results and Pichler and Beirne's, LS had the highest incidence of temporary LNI followed by BA+ and then BA-. However, the prevalence of BA-found by Pichler and Beirne was lower while BA+ and LS were higher [12].
The prevalence of permanent LNI following BA-, BA+ and LS was 0.18%, 0.07%, and 0.28% respectively. There is an increased prevalence of permanent LNI following the use of LS compared to both BA-and BA+. These results were inconsistent with Pichler and Beirne who found that LS had the lowest prevalence of permanent LNI while BA+ had the highest [0.2% (BA-), 0.6% (BA+), 0.1% (LS)] [12]. This discrepancy may be due to insufficient data being available regarding permanent LNI.
Our study had negligible statistical heterogeneity. Quantifying statistical heterogeneity can only be validated if there is an unknown clinical heterogeneity [49]. According to the overall RR in this study, it is most likely that there was no evidence of clinical heterogeneity. Furthermore, according to our systematic review, clinical covariates across all studies (e.g. patient level, intervention level, outcome level) are shown to be similar. This was as a result of the stringent criterion placed to minimise heterogeneity [50]. Furthermore, during the derivation of the forest plot, implementing both fixed-and random-effects model made little difference to the I 2 value.

Limitations
One of the major limitations of this systematic review and meta-analysis was that we were unable to calculate the risk ratio for permanent LNI due to the lack of published data. Furthermore, only the RR between BA+ versus BA-was calculated as there was insufficient data to  calculate for LS to draw a statistically meaningful conclusion. Another limitation was the exclusion of grey literature from our study; however, the inclusion of grey literature may have further skewed our results due to the lack of peer review within these studies. In addition, many studies were not randomised controlled trials. In many studies, the use of a lingual retractor was used at the clinician's discretion. This could introduce a level of bias as it may indicate that lingual retraction was used in more difficult cases that were at higher risk of LNI regardless of whether lingual retraction was used or not. Another limitation was that the type of lingual retractor used varied between the articles and some articles did not specify what was used ( Table 2). This may introduce a level of bias as Rapaport and Brown found that the percentage risk of permanent LNI was lowest when purpose-built lingual retractors were used [13]. They also found that the use of repurposed lingual retractors had the highest risk of temporary and permanent LNI. Another limitation was the position and impaction of the M3M were not factored in when comparing the incidence of LNI. The position of the M3M has been noted to affect the risk of LNI [51]. However, we were unable to analyse this factor as the studies included in our systematic review did not outline the impaction of the M3M. This could be something that could potentially be explored in the future. Lastly, limitations were also present during data input. When papers did not list the number of subjects or teeth, we adopted a 1:1 ratio for subject:patient when inputting the data. This could potentially skew the results if studies had one patient undergoing two M3M surgical extractions.

Implication of practice
The global prevalence of impacted M3M is approximately 24% [52]. In 2008, an estimated number of hospitalisations for extraction of impacted M3M in Australia was 97,949 [15-34  years]. This resulted in the total cost of $531 million AUD [53]. In addition, in the United States, approximately 10 million M3M were extracted annually with costs approximating $3 billion USD [54]. One of the risks of M3M is LNI which can negatively impact a patient's QoL [1], and therefore operators should attempt to minimise the risk as much as possible. Previous studies have used lingual retraction to protect the lingual nerve from injury. As there are limited studies that published the outcomes of permanent LNI, further research is required to assess and analyse the incidence of permanent LNI following these techniques (BA-, BA+, and LS).

Conclusion
This study has shown that there is a quantifiable increased risk of temporary LNI following the surgical extraction of M3M when BA+ and LS is used compared to BA-. The current literature showed that there was a lower incidence of permanent LNI after using BA+ compared to BAand LS. LS had a higher temporary and permanent risk for LNI. There is insufficient evidence to determine whether there is a significant advantage of lingual nerve retraction for reducing the risk of permanent LNI despite the low incidence. Larger scale studies are needed to consolidate the findings. Operators should use BA+ and LS with caution due to the increased risk of temporary LNI. Were measures undertaken to address and categorise non-responders? 2 2 0 23 Were the risk factor and outcome variables measured appropriate to the aims of the study? 27 0 0 0 Were the risk factor and outcome variables measured correctly using instruments/measurements that had been trialled, piloted or published previously? 10 17 0 0 Is it clear what was used to determine statistical significance and/or precision estimates? 16 5 0 6 Were the methods (including statistical methods) sufficiently described to enable them to be repeated? 20 7 0 0

Results
Were the basic data adequately described? 26 1 0 0 Does the response rate raise concerns about non-response bias? 0 27 0 0 If appropriate, was information about non-responders described? 2 2 0 23 Were the results internally consistent? 1 25 0 1 Were the results presented for all the analyses described in the methods? Supporting information S1 Checklist. PRISMA 2020 checklist. (DOCX)